There are two principle classes of lymphocytes involved in the immune system of humans and animals. B cells develop from haemopoietic stem cells in the bone marrow and remain in the bone marrow to undergo differentiation. Mature B cells emerge from the bone marrow and circulate freely in the body humors. B cells secrete antibodies and are responsible for humoral immune responses.
T cells likewise develop from haemopoietic stem cells in the bone marrow, but are differentiated in the thymus. Mature T cells emerge from the thymus and circulate between the tissues, lymphatics and bloodstream where they form a large percentage of the pool of recirculating small lymphocytes. They exhibit immunological specificity and are directly involved as effector cells in cell-mediated immune responses, such as graft rejection. T cells do not secrete antibodies.
It is now recognized that circulating T cells are divided into several subtypes, termed "helper," "suppressor" and "killer" T cells which have the functions of promoting a reaction, suppressing a reaction or killing (lysing) foreign cells, respectively. It is further recognized that, within these subtypes, various subsets or subpopulations exist. Circulating T cells are generally nonproliferative and are commonly referred to as nonactivated, unstimulated, resting or normal cells. In this disclosure, such nonproliferating T cells are hereinafter referred to as resting T cells. Under some circumstances, for example, when in the presence of a specific antigen such as Leu 4, or a mitogen, T cells do proliferate. Proliferating T cells are generally referred to as activated cells. Activation of T cells results in expression of surface antigens not expressed by normal cells.
The ability to identify and enumerate classes, types and subsets of T-lymphocytes is important for diagnosis or treatment of various immunoregulatory disorders. For example, rheumatoid arthritis and malignancies are associated with an imbalance of T cell subsets.
The identification and suppression of human T cell classes and subclasses have been accomplished by using isolated autoantibodies or polyclonal antisera for human T cells. Such preparations have all the disadvantages, such as heterogeneity and unwanted side reactions, associated with polyclonal antibodies.
Monoclonal antibodies to resting T cells have been described. U.S. Pat. Nos. 4,515,893 and 4,515,894 to Kung et al. disclose monoclonal antibodies which react with essentially all resting human peripheral T cells. U.S. Pat. No. 4,515,895 to Kung et al. discloses monoclonal antibodies which react with essentially all resting human peripheral helper T cells. U.S. Pat. No. 4,364,932 to Kung et al. discloses monoclonal antibodies which react with the cytotoxic and suppressor T cell subset designated as TH.sub.2.sup.+. A monoclonal antibody which binds specifically to the surface recognition structure of a human T cell clone is disclosed in U.S. Pat. No. 4,550,086 to Reinherz et al. A monoclonal antibody which recognizes a surface glycoprotein on proliferating blood cells which is absent on normal peripheral blood cells is disclosed in U.S. Pat. No. 4,626,507 to Trowbridge et al.
There is a need for a method to demonstrate or detect activated T lymphocytes and/or subsets thereof, whereby conditions such as autoimmune diseases and transplantation reactions may be monitored. The present invention provides such a method and also monoclonal antibodies for fulfilling this need.